Human postmortem studies reveal tissue-specific differences amongst TB-patient groups

Abstract

AbstractIf we are to break new grounds in TB research, we need to have a complete understanding of what is occurring at the site of infection in humans. Postmortem studies give us an opportunity to compare TB-involved and -uninvolved tissues, in both diseased and non-diseased individuals. We examined the feasibility of carrying out a postmortem study in Mulago and Kiruddu National Referral Hospitals in Uganda, to determine whether we could use immune cells collected postmortem for immunological studies. We report that we can consent the Next-of-Kin, perform postmortem procedures and process tissues within 8 hours of death, and that immune cells remain viable and functional up to 14 hours after death. We found subtle differences in T cell subsets within TB groups. We found a depletion of the CD4 CD69+CD103+T cell subset in the lungs and BAL, which was associated with HIV, and that the CD8 CD69+CD103-T cell subset was depleted in BAL only, and was associated with TB. Our data show overall changes Tissue Resident Memory T cells within, and between, TB-infected and TB-uninfected human lungs.SummaryCoroner led postmortem studies are possible in Uganda, samples processed within 8 hours from deathCells from samples collected postmortem are viable and functionalHIV associated depletion of CD4 CD69+/CD103+T cell subset in lungs and BALCD8 CD69+/CD103-depletion in BAL associated with TB